The Effect of Mesenchymal Stem Cells on Fertility in Experimental Retrocervical Endometriosis / O efeito das células-tronco mesenquimais na fertilidade em endometriose retrocervical experimental

Abstract Purpose To evaluate the effect of mesenchymal stem cells (MSCs) on fertility in experimental retrocervical endometriosis. Methods A total of 27 New Zealand rabbits were divided into three groups: endometriosis, in which endometrial implants were created; mesenchymal, in which MSCs were applied in addition to the creation of endometrial implants; and control, the group without endometriosis. Fisher's exact test was performed to compare the dichotomous qualitative variables among the groups. The quantitative variables were compared by the nonparametric Mann-Whitney and Kruskal-Wallis tests. The MannWhitney test was used for post-hoc multiple comparison with Boniferroni correction. Results Regarding the beginning of the fertile period, the three groups had medians of 14±12.7, 40±5, and 33±8.9 days respectively (p = 0.005). With regard to fertility (number of pregnancies), the endometriosis and control groups showed a rate of 77.78%, whereas the mesenchymal group showed a rate of 11.20% (p = 0.015). No differences in Keenan's histological classification were observed among the groups (p = 0.730). With regard to the macroscopic appearance of the lesions, the mesenchymal group showed the most pelvic adhesions. Conclusion The use of MSCs in endometriosis negatively contributed to fertility, suggesting the role of these cells in the development of this disease.

Resumo Objetivo Avaliar o efeito das células-tronco mesenquimais sobre a fertilidade na endometriose retrocervical experimental. Métodos Um total de 27 coelhas da raça Nova Zelândia foram divididas em três grupos: endometriose, em que os implantes endometriais foram criados; mesenquimal, em que as células-tronco mesenquimais foram aplicadas complementarmente à criação implantes endometriais; e controle, sem endometriose. O teste exato de Fisher foi realizado para comparar variáveis dicotômicas qualitativas entre os grupos. As variáveis quantitativas foram comparadas pelos testes não paramétricos de MannWhitney e Kruskal-Wallis. O teste de Mann-Whitney foi utilizado para a comparação múltipla pós-hoc com correção de Boniferroni. Resultados em relação ao início do período fértil, os grupos endometriose, mesenquimal e controle tiveram medianas de 14±12,7; 40±5; e 33±8,9 dias, respectivamente (p = 0,005). Sobre a taxa de fertilidade (número de gravidezes), os grupos endometriose e controle mostraram uma taxa de 77,78%, enquanto o grupo mesenquimal mostrou uma taxa de 11,20% (p = 0,015). Não foram observadas diferenças na classificação histológica de Keenan entre os grupos (p = 0,730). No que diz respeito à aparência macroscópica das lesões, o grupo mesenquimal mostrou maiores adesões pélvicas. Conclusão O uso de células-tronco mesenquimais na endometriose contribuiu negativamente para a fertilidade, sugerindo o papel dessas células no desenvolvimento da doença.

Evaluating PCR, culture & histopathology in the diagnosis of female genital tuberculosis.

Background & objectives: Genital tuberculosis (GTB) is one of the major causes for severe tubal disease leading to infertility. Unlike pulmonary tuberculosis, the clinical diagnosis of GTB is difficult because in majority of cases the disease is either asymptomatic or has varied clinical presentation. Routine laboratory values are of little value in the diagnosis. An absolute diagnosis cannot be made from characteristic features in hysterosalpingogram (HSG) or laparoscopy. Due to the paucibacillary nature of GTB, diagnosis by mycobacterial culture and histopathological examination (HPE) have limitations and low detection rate. The objective of this study was to evaluate the efficacy of PCR technique, culture and histopathological examination in the diagnosis of GTB in female infertility. Methods: This study included 72 infertile women who met the inclusion and exclusion criteria. After a detailed history and clinical examination all patients were subjected to investigations including pelvic sonogram, HSG and laparoscopy. Endometrial samples from were allocated for AFB smear, culture and HPE examination. Only 49 samples were available for PCR using IS 6110 and TRC4 primers. In seven patients peritoneal fluid was also taken for culture and PCR. Based on the clinical profile and laparoscopic findings, a diagnostic criteria was derived to suspect GTB. Specific diagnostic tests were evaluated against this diagnostic criterion. Results: Laparoscopy was suggestive of tuberculosis in 59.7 per cent of cases, AFB smear was positive in 8.3 per cent, culture was positive in 5.6 per cent, HPE positive in 6.9 per cent and PCR was positive in 36.7 per cent of cases. Based on the diagnostic criteria, GTB was suspected in 28 of the 49 cases. On evaluating against the diagnostic criteria, the sensitivity of PCR, HPE and culture were 57.1, 10.7, 7.14 per cent respectively. The concordance of results between the clinical criteria and specific diagnostic tests were analysed by Kappa measure of agreement. The culture and HPE showed mild agreement with the clinical criteria, whereas PCR showed a moderate agreement. PCR was positive in Two of the 21 cases in whom GTB was not suspected. False positive PCR in these two cases were ruled out by multiple areas of sampling and re-sampling in one case. The PCR results were negative in 12 of the 28 cases. PCR using TRC4 primers had a higher sensitivity (46.4%) than IS 6110 primers (25%) in detecting clinically suspected GTB. Interpretation & conclusions: Our results showed that conventional methods of diagnosis namely, HPE, AFB smear and culture have low sensitivity. PCR was found to be useful in diagnosing early disease as well as confirming diagnosis in clinically suspected cases. False negative PCR was an important limitation in this study.

Dolor pélvico crónico e infertilidad como factores diagnósticos de endometriosis / Chronic pelvic pain and infertility as diagnostic factors of endometriosis

Determinar si los síntomas de dolor pélvico crónico y/o la infertelidad, son importantes en el diagnóstico precoz de endometriodid. Análisis retrospectivo de 100 pacientes con diagnóstico por laparoscopia de endometriosis, divididas en dos grupos: Grupo I constituido por 40 pacientes con el dolor pélvico crónico y el Grupo 2 con 60 pacientes con dolor pélvico e infertilidad, en el período enero 2002 a enero 2005. Hospital Coromoto, Maracaibo, Estado Zulia, Venezuela. El promedio de edad en la primera consulta fue de 26.5 y 34.6 años para los grupos 1 y 2 respectivamente. Se encontró un 74 por ciento de dispareunia profunda en ambos grupos. La sintomatología gastrointestinal en las pacientes del Grupo 1 se detectó en 28 por ciento y en las del Grupo 2 en el 38 por ciento, en distintos grados. El síndrome premenstrual y/o alteraciones emocionales, se presentaron en el 80 por ciento de las pacientes y el patrón también fue de moderado a severo. El estadio de la enfermedad valorado por laparoscopia, demostró que el nivel del dolor pélvico crónico no está relacionado con el de la enfermedad, pero sí con su ubicación anatómica, y la más dolorosa fue cuando se ubica en los ligamentos uterosacrales, y en el fondo de saco posterior. En las pacientes del Grupo 1 se presentó con mayor frecuencia el grado IV (12 por ciento), seguido del grado II (11 por ciento). En las pacientes del Grupo 2 los grados más frecuentes fueron el II (22 por ciento) y el I (18 por ciento). En las pacientes del Grupo 2 los grados más frecuentes fueron el II (22 por ciento) y el I (18 por ciento). En el 50 por ciento de las pacientes no se realizó estudio histopatológico. El dolor pélvico crónico es más frecuente en mujeres jóvenes que presentan endometriosis, mientras que la infertilidad se presenta con mayor frecuencia en el grupo de pacientes de mediana edad. Amedida que se avanza en edad, la probabilidad de encontrar infertilidad y dolor pélvico aumenta.

Comparison of hysterosalpingography and laparoscopy in the evaluation of infertile women

To compare tuboperitoneal factors of infertile women by hysterosalpingography [HSG] and laparoscopy. In this cohort study, 82 infertile cases were evaluated retrospectively by laparoscopy, 3 months subsequent to HSG in the Department of Gynecology and Obstetrics, Medical School of Dicle University, Diyarbakir, Turkey, between March 2004 and April 2006. The findings of HSG and laparoscopy were compared. Out of the 82 infertile women, pathological findings were observed in 45.1% by HSG, and 54.9% had no pathological finding. On laparoscopic evaluation, however, pathological findings were observed in 65.85%, and 34.15% had no pathological findings. The pathological findings were detected by laparoscopy in 20 of the 45[44.4%] patients who had no pathological findings by HSG, and no pathological findings were detected by laparoscopy in 3 of the 37 [8.1%] patients who had pathological findings by HSG. Laparoscopy revealed no pathological findings in 6 of the 35 patients who had tubal pathology by HSG. The sensitivity of HSG was 63%, specificity was 89.3%, and the positive predictive value was 92%, with a 55% predictive value, and the accuracy ratio was 72%. Laparoscopy is a superior method for the research of tubal and pelvic pathologies in the evaluation of infertility. However, HSG is a more economical and elementary method suitable for evaluation of endometrial and tubal pathologies, and laparoscopy is an appropriate method for examining the external part of tubae, fimbriae, the relation of tuba and ovary, endometriosis, adhesions, tuberculosis, and other pathologies. Therefore, these 2 methods are not alternative, but complementary

spectrum of histopathological findings in endometrial curettage submitted from infertile women

This is a retrospective study done on 523 consecutive women with infertility during for period from 1991 up to 1995. Our purpose of this study is to know the most frequent type of infertility, endometrial changes and the age group affected. We found that the primary infertility is the most common and represented 70.17% of the cases, while secondary infertility is 29.83%. The most predominant histopathological finding in both types of infertility is secretary endometrium which is 61.57%, followed by proliferative endometrium 20.46% then endometrial hyperplasia 8.60%. The majority of the women in our study group did not have their age specified. They represent 56.98% of all women under study. Most of the primary infertility cases were in the 20 age group [21.61%] and secondary infertility in 30 age group [6.50%]. We concluded that primary infertility is the most common type of infertility and it affects the younger age group. The highest percentages of these women have ovulation

Validez de la videolaparoscopía respecto a la evaluación histológica de lesiones sospechosas de endometriosis en mujeres con esterilidad / Videolaparoscopy versus histopathology in evaluation of suspect endometriosis lesion in woman with sterility

La endometriosis es el padecimiento más frecuente encontrado en mujeres sometidas a laparoscopía. A pesar de su frecuencia, existe una importante controversia mundial con respecto al pronóstico, diagnóstico y tratamiento. Objetivo. Evaluar la capacidad diagnóstica de la videolaparoscopía en lesiones sospechosas de endometriosis y su correlación histológica, así como determinar si la experiencia de los cirujanos modifica el diagnóstico de esta entidad. Materia y método. Se tomaron biopsias peritoneales de 45 pacientes sometidas a laparoscopía, en el periodo del 1 de junio de 1993 al 31 de enero de 1994. La biopsia fue enviada a histopatología. Las lesiones que contenían glándulas y estroma, fueron calificadas como endometriosis. El grupo I (n=25) pacientes con endometriosis y el grupo II (n=20) con peritoneo normal. Las laparoscopías fueron grabadas en videocasettes. Cada video fue sometido a la interpretación diagnóstica de médicos residentes de 3§, 4§ y 5§ año, médicos adscritos y jefe de servicio. Resultados. Se efectuaron un total de 225 evaluaciones a través de la videolaparoscopía. Estas fueron analizada por el teorema de Bayes, para determinar la especificidad, sensibilidad, valores predictivos positivos y negativos, la confiabilidad y la prevalencia. La sensibilidad y especificidad promedio fue de 68.4 por ciento y de 73.1 por ciento resepectivamente. El valor predictivo positivo fue de 70.3 por ciento y el negativo de 72.1 por ciento, con una confibilidad de 70.9 por ciento. Estos valores significan que en 31.6 por ciento de los casos no se hizo diagnóstico y en 26.9 por ciento se diagnóstico equivocadamente la enfermedad. Se destaca además que la experiencia del cirujano influyó postivamente en la identificación de la entidad, con una sensibilidad de 76.1 por ciento y una especificidad de 95.8 por ciento. conclusiones. Este estudio permite confirmar que la comprobación histopatológica de la endometriosis es indispensable y que la apreciación visual laparocópica de lesiones sospechosas de endometriosis conducirá a un importante porcentaje de pacientes sin diagnóstico, el mismo tiempo que el sobrediagnóstico en 27 por ciento de los casos

Distúrbios da fase pós-ovulatória e funçäo endometrial: um estudo clínico em esterilidade / Postovulatory phase disturbances and endometrial function: a clinical study in sterility

Estabelecemos protocolo que permitiu avaliar a eficácia do intervalo menstrual e de duas dosagens seriadas de progesterona (P) e prolactina (PRL) no diagnóstico dos distúrbios da fase lútea. Estudamos 52 clientes com fertilidade prévia comprovada e outras 79 inférteis. Todas foram submetidas à biópsia endometrial, que foi usada como padräo-ouro na avaliaçäo dos testes estatísticos realizados. O datamento endometrial mostrou 55,8 por cento do endométrio secretor normal na populaçäo fértil, contra 27,8 por cento na populaçäo infertil. Houve 45,6 por cento de endométrio secretor deficiente do tipo dissociado entre as inférteis, de acordo com a classificaçäo de Dallenbach-Hellweg. Das 79 clientes inférteis, 42 foram submetidas à colheita de duas amostras para dosagens de P e PRL no meio da fase lútea e três dias após. O intervalo menstrual mostrou-se altamente específico, ou seja, quando de 28-30 dias raramente está associado à fase lútea deficiente. O valor preditivo positivo dos valores de P foi de 82 por cento, näo havendo diferença significativa entre os dias de colheita ou diferentes níveis de corte avaliados (< 2,3 ou ó 5ng/ml). A somatória das dosagens seriadas näo trouxe qualquer vantagem em relaçäo à dosagem única. O valor preditivo positivo da dosagem de PRL foi de 77 por cento, näo havendo diferenças significativas também entre os dias de colheita, pontos de corte ( < 2,6 ou ò 25ng/ml < 2,6 ou ò 15ng/ml ) ou avaliaçäo de quaisquer níveis alterados. Entretanto, a sensibilidade na avaliaçäo individual das colheitas favoreceu o ponto de corte que inclui valores alterados < 2,6 e ò 15 ng/ml. As dosagens hormonais mostram-se eficazes na avaliaçäo do funcionamento do corpo lúteo e podem substituir a biópsia de endométrio quando ela näo é possível de ser realizada

Correlaçäo entre o desenvolvimento endometrial e o nível sérico de progesterona na fase lútea de pacientes com ciclos ovulatórios / Correlation between endometrial development and luteal phase serum progesterone in patients with ovulatory cicles

Foi verificada a relaçäo entre o valor plasmático de progesterona na fase lútea média e a maturaçäo histológica do endométrio em 21 mulheres com queixa de infertilidade e ovulaçäo documentada por ultra-sonografia e dosagens hormonais seriadas. Mostoru-se que em todas as pacientes as medidas de progesterona na fase lútea média se encontravam dentro dos limites considerados normais. Apesar disto, em 43 por cento das pacientes o grau de maturidade endometrial era inadequado, o que permite concluir pela necessidade da avaliaçäo da maturidade endometrial na pesquisa de infertilidade da mulher

El factor ovánico endocrino en infertilidad matrimonial / Ovarian-Endocrine Factor In Infertility marriyes

Se realizó un estudio retrospectivo en mujeres con infertilidad de origen ovárico endocrino en el Hospital Arzobispo Loayza entre enero de 1983 y Setiembre de 1991, encontrándose 138 casos que corresponden a una incidencia del 22.4 por ciento de las pacientes infértiles, representando un incremento de dicha patología en nuestro medio. La entidad más frecuente fue la Anovulacián crónica de causa indeterminada con un 31.87 por ciento, seguida por el Sindrome de ovario poliquístico con 18.84%, la Hiperprolactinemia con 18.12 por ciento, y la Fase lútea inadecuada con 17.38 por ciento. Estas tres entidades han aumentado su incidencia a expensas de la Anovulación crónica de causa indeterminada, debido a las mayores facilidades para su diagnóstico. El 61.59 por ciento tuvo irregularidades mestruales, siendo las más frecuentes la oligomenorrea, y la amenorrea, presentes ambas en el 28.26 por ciento de las pacientes. Las causas más importantes de oligomenorrea fueron la Anovulación crónica de causa indeterminada, con 51.28 por ciento, y la poliquistosis ovárica, con 30.77 por ciento, y de amenorrea la Hiperprolactinemia con 35.9 por ciento. El 83.33 por ciento de las pacientes con Fase lútea inadecuada tuvo ciclos clinicamente regulares

Pap smear examinations of infertile women.

Pap smear examinations of 139 infertile women taken between June 19, 1983 and December 26, 1983 were studied at the Cytological Room, Department of Obstetrics & Gynaecology, Faculty of Medicine, Siriraj Hospital, Mahidol University. The range of age was 17 to 44 years, the mean age being 28.2 +/- 4.9 years. The percentage of cytological findings were: 84.9 normal women, 10.1 hormonal abnormality (of those with non-normal hormone, 7.2 of the total had a mild degree of abnormality), 5.0 no hormonal evaluation, 1.4 few abnormal cells and 0.7 folic acid deficiency.

Histochemical Studies of Human Endometrium with Special Emphasis on Secretory Activity and Ovulation

Eighty eight cases of the endometrial biopsy comprising 19 cases of proliferative phase, 21 cases of secretory phase, and 23 cases of menstrual phase from non-sterility patients, and 25 cases of the endometrium at the first day of menstruation from primary sterility patients were examined histochemically. Secretory substance in the epithelial cells of the endometrial glands during the secretory phase and menstrual phase was main1y glycogen. Therefore, it is essential to fix the endometrial tissue in a fixative which can preserve glycogen for the detection of secretory activity more accurately. Among 25 cases of primary sterility, 15 cases showed epithelial secretory vacuoles on hematoxylin and eosin stained sections, and no epithelial vacuolization was noted in the remaining 10 cases. However, PAS staining showed presence of PAS positive diastase sensitive substance in the majority of the later 10 cases except one in which no PAS positive substance was found, indicating that PAS staining is superior than routine hematoxylin and eosin staining for the detection of epithelial secretory substance. The absolute lack of secretory activity in the endometrial glands was infrequent, but a relative decrease of progesterone effect was rather common among the patients complaining primary sterility, and the decreased progesterone effect may not necessarily be due to the absence of ovulation.